tbuckley/cabot-search huggingface dataset:
Validation of epidermal AMBRA1 and loricrin (AMBLor) as a prognostic biomarker for nonulcerated American Joint Committee on Cancer stage I/II cutaneous melanoma
Authors: Tom Ewen, Akhtar Husain, Niki Stefanos, Paul Barrett, Claire Jones, Tom Ness, Anna Long, Stuart Horswell, Helen Bosomworth, Joe Lowenstein, Grant Richardson, David Swan, Ashleigh McConnell, Aidan Rose, Tom Andrew, Nick Reynolds, Josep Malvehy, Christina Carrera, Llucia Alos, Sonia Mailer, Thomas Helm, Liang Ding, Paul Bogner, Sebastian Podlipnik, Susana Puig, Grant A McArthur, Gyorgy Paragh, Marie Labus, Philip Sloan, Jane L Armstrong, Penny E Lovat
Journal: British Journal of Dermatology (2023)

Abstract Background Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of ­metastasis. Objectives To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence. Methods Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined. Results Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P &amp;lt; 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P &amp;lt; 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403–8.580, P = 0.007) and an overall NPV of 96.5%. Conclusions These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence.
Calprotectin in Parkinsonian disease: Anticipation and dedication
Authors: Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Ayah Talal Zaidalkiani, Athanasios Alexiou, Marios Papadakis, Mostafa M. Bahaa, Ammar AL-Faraga, Gaber El-Saber Batiha
Journal: Ageing Research Reviews (2023)
Immune-Related Toxicity in NSCLC: Current State-of-the-Art and Emerging Clinical Challenges
Authors: Caroline L O'Leary, Nicole Pierce, Sandip P Patel, Jarushka Naidoo
Journal: Journal of Thoracic Oncology (2023)

Immune checkpoint inhibitors have become standard-of-care for the treatment of NSCLC; however, their use brings with it the risk of a unique set of inflammatory side effects, termed immune-related adverse events (irAEs). The recognition, diagnosis, and management of irAEs have become essential to clinical practice, with the potential for high-grade toxicities affecting treatment decision-making. This manuscript provides a state-of-the-art review of irAEs as they pertain to patients with NSCLC, by summarizing the common and severe toxicities of the standard immune checkpoint inhibitor regimens and clinical treatment settings relevant to this disease and future directions.
Real-World Efficacy and Safety of Amivantamab for EGFR-Mutant NSCLC
Authors: Kaiwen Wang, Robyn Du, Nathaniel J. Myall, Whitney E. Lewis, Natalie Uy, Lingzhi Hong, Ferdinandos Skoulidis, Lauren A. Byers, Anne Tsao, Tina Cascone, Jenny Pozadzides, Janet Tu, Marcelo V. Negrao, Don L. Gibbons, Keunchil Park, Waree Rinsurongkawong, J. Jack Lee, David Gandara, Deepti Behl, Catherine A. Shu, Jonathan W. Riess, Christina Baik, Heather A. Wakelee, Ara A. Vaporciyan, John V. Heymach, Jianjun Zhang, Xiuning Le
Journal: Journal of Thoracic Oncology (2023)

Amivantamab-vmjw (amivantamab) is a bispecific EGFR/MET antibody approved for patients with advanced NSCLC with EGFR exon 20 insertion mutations, after prior therapy. Nevertheless, the benefits and safety of amivantamab in other EGFR-mutant lung cancer, with or without osimertinib, and with concurrent radiation therapy, are less known. We queried the MD Anderson Lung Cancer GEMINI, Fred Hutchinson Cancer Research Center, University of California Davis Comprehensive Cancer Center, and Stanford Cancer Center's database for patients with EGFR-mutant NSCLC treated with amivantamab, not on a clinical trial. The data analyzed included initial response, duration of treatment, and concomitant radiation safety in overall population and prespecified subgroups. A total of 61 patients received amivantamab. Median age was 65 (31-81) years old; 72.1% were female; and 77% were patients with never smoking history. Median number of prior lines of therapies was four. On the basis of tumor's EGFR mutation, 39 patients were in the classical mutation cohort, 15 patients in the exon 20 cohort, and seven patients in the atypical cohort. There were 37 patients (58.7%) who received amivantamab concomitantly with osimertinib and 25 patients (39.1%) who received concomitant radiation. Furthermore, 54 patients were assessable for response in the overall population; 19 patients (45.2%) had clinical response and disease control rate (DCR) was 64.3%. In the classical mutation cohort of the 33 assessable patients, 12 (36.4%) had clinical response and DCR was 48.5%. In the atypical mutation cohort, six of the seven patients (85.7%) had clinical response and DCR was 100%. Of the 13 assessable patients in the exon 20 cohort, five patients (35.7%) had clinical response and DCR was 64.3%. Adverse events reported with amivantamab use were similar as previously described in product labeling. No additional toxicities were noted when amivantamab was given with radiation with or without osimertinib. Our real-world multicenter analysis revealed that amivantamab is a potentially effective treatment option for patients with EGFR mutations outside of exon 20 insertion mutations. The combination of osimertinib with amivantamab is safe and feasible. Radiation therapy also seems safe when administered sequentially or concurrently with amivantamab.
Riemannian frameworks for the harmonization of resting-state functional MRI scans
Authors: Nicolas Honnorat, Sudha Seshadri, Ron Killiany, John Blangero, David C. Glahn, Peter Fox, Mohamad Habes
Journal: Medical Image Analysis (2023)

Magnetic Resonance Imaging provides unprecedented images of the brain. Unfortunately, scanners and acquisition protocols can significantly impact MRI scans. The development of statistical methods able to reduce this variability without altering the relevant information in the scans, often coined harmonization methods, has been the topic of an increasing research effort supported by the recent growth of publicly available neuroimaging data sets and new possibilities for combining them to achieve greater statistical power. In this work, we focus on the challenges specifically raised by the harmonization of resting-state functional MRI scans. We propose to harmonize resting-state fMRI scans by reducing the impact of covariates such as scanner differences and scanning protocols on their associated functional connectomes and then propagating the changes back to the rs-fMRI time series. We use Riemannian geometric frameworks to preserve the mathematical properties of functional connectomes during their harmonization, and we demonstrate how state-of-the-art harmonization methods can be embedded within these frameworks to reduce covariates effects while preserving the relevant clinical information associated with aging or brain disorders. During our experiments, a large set of synthetic data was generated and processed to compare eighty variants of the proposed approach. The framework achieving the best harmonization was then applied to three low-dimensional data sets made of 712 sets of fMRI time series provided by the ABIDE consortium and two high-dimensional data sets obtained by processing 1527 rs-fMRI scans provided by the Human Connectome Project, the Framingham Heart Study and the Genetics of Brain Structure and Function study. These experiments established that our new framework could successfully harmonize low-dimensional connectomes and voxelwise functional time series and confirmed the need for preserving connectomes properties during their harmonization.
Guidelines for cold urticaria management established by the Centre of Evidence of Dermatology and the Urticaria Group of the French Society of Dermatology
Authors: Alice Bréhon, Lynda Bensefa-Colas, Cyril D’Andrea, Eric Jeziorski, Marie-Pascale Lehucher-Michel, Johan Lequipe, Nicolas Marmion, Pascale Mathelier-Fusade, Jean-Christophe Mercier, Georges Sebatigita, Julio Tannous, Martine Vigan, Bernard Guillot, Aurélie Du-Thanh, Angèle Soria
Journal: British Journal of Dermatology (2023)

This research letter provides guidelines for cold urticaria management established by the Centre of Evidence of Dermatology and the Urticaria Group of the French Society of Dermatology.
Subgenomic Stability of Progenitor Genomes During Repeated Allotetraploid Origins of the Same Grass <i>Brachypodium hybridum</i>
Authors: Wenjie Mu, Kexin Li, Yongzhi Yang, Adina Breiman, Jiao Yang, Ying Wu, Mingjia Zhu, Shuai Wang, Pilar Catalan, Eviatar Nevo, Jianquan Liu
Journal: Molecular Biology and Evolution (2023)

Both homeologous exchanges and homeologous expression bias are generally found in most allopolyploid species. Whether homeologous exchanges and homeologous expression bias differ between repeated allopolyploid speciation events from the same progenitor species remains unknown. Here, we detected a third independent and recent allotetraploid origin for the model grass Brachypodium hybridum. Our homeologous exchange with replacement analyses indicated the absence of significant homeologous exchanges in any of the three types of wild allotetraploids, supporting the integrity of their progenitor subgenomes and the immediate creation of the amphidiploids. Further homeologous expression bias tests did not uncover significant subgenomic dominance in different tissues and conditions of the allotetraploids. This suggests a balanced expression of homeologs under similar or dissimilar ecological conditions in their natural habitats. We observed that the density of transposons around genes was not associated with the initial establishment of subgenome dominance; rather, this feature is inherited from the progenitor genome. We found that drought response genes were highly induced in the two subgenomes, likely contributing to the local adaptation of this species to arid habitats in the third allotetraploid event. These findings provide evidence for the consistency of subgenomic stability of parental genomes across multiple allopolyploidization events that led to the same species at different periods. Our study emphasizes the importance of selecting closely related progenitor species genomes to accurately assess homeologous exchange with replacement in allopolyploids, thereby avoiding the detection of false homeologous exchanges when using less related progenitor species genomes.
Developing natural polymers for skin wound healing
Authors: Han Zhang, Xiang Lin, Xinyue Cao, Yu Wang, Jinglin Wang, Yuanjin Zhao
Journal: Bioactive Materials (2023)

Natural polymers are complex organic molecules that occur in the natural environment and have not been subjected to artificial synthesis. They are frequently encountered in various creatures, including mammals, plants, and microbes. The aforementioned polymers are commonly derived from renewable sources, possess a notable level of compatibility with living organisms, and have a limited adverse effect on the environment. As a result, they hold considerable significance in the development of sustainable and environmentally friendly goods. In recent times, there has been notable advancement in the investigation of the potential uses of natural polymers in the field of biomedicine, specifically in relation to natural biomaterials that exhibit antibacterial and antioxidant characteristics. This review provides a comprehensive overview of prevalent natural polymers utilized in the biomedical domain throughout the preceding two decades. In this paper, we present a comprehensive examination of the components and typical methods for the preparation of biomaterials based on natural polymers. Furthermore, we summarize the application of natural polymer materials in each stage of skin wound repair. Finally, we present key findings and insights into the limitations of current natural polymers and elucidate the prospects for their future development in this field.
GITR and TIGIT immunotherapy provokes divergent multicellular responses in the tumor microenvironment of gastrointestinal cancers
Authors: Anuja Sathe, Carlos Ayala, Xiangqi Bai, Susan M. Grimes, Byrne Lee, Cindy Kin, Andrew Shelton, George Poultsides, Hanlee P. Ji
Journal: Genome Medicine (2023)

Abstract Background Understanding the mechanistic effects of novel immunotherapy agents is critical to improving their successful clinical translation. These effects need to be studied in preclinical models that maintain the heterogenous tumor microenvironment (TME) and dysfunctional cell states found in a patient’s tumor. We investigated immunotherapy perturbations targeting co-stimulatory molecule GITR and co-inhibitory immune checkpoint TIGIT in a patient-derived ex vivo system that maintains the TME in its near-native state. Leveraging single-cell genomics, we identified cell type-specific transcriptional reprogramming in response to immunotherapy perturbations. Methods We generated ex vivo tumor slice cultures from fresh surgical resections of gastric and colon cancer and treated them with GITR agonist or TIGIT antagonist antibodies. We applied paired single-cell RNA and TCR sequencing to the original surgical resections, control, and treated ex vivo tumor slice cultures. We additionally confirmed target expression using multiplex immunofluorescence and validated our findings with RNA in situ hybridization. Results We confirmed that tumor slice cultures maintained the cell types, transcriptional cell states and proportions of the original surgical resection. The GITR agonist was limited to increasing effector gene expression only in cytotoxic CD8 T cells. Dysfunctional exhausted CD8 T cells did not respond to GITR agonist. In contrast, the TIGIT antagonist increased TCR signaling and activated both cytotoxic and dysfunctional CD8 T cells. This included cells corresponding to TCR clonotypes with features indicative of potential tumor antigen reactivity. The TIGIT antagonist also activated T follicular helper-like cells and dendritic cells, and reduced markers of immunosuppression in regulatory T cells. Conclusions We identified novel cellular mechanisms of action of GITR and TIGIT immunotherapy in the patients’ TME. Unlike the GITR agonist that generated a limited transcriptional response, TIGIT antagonist orchestrated a multicellular response involving CD8 T cells, T follicular helper-like cells, dendritic cells, and regulatory T cells. Our experimental strategy combining single-cell genomics with preclinical models can successfully identify mechanisms of action of novel immunotherapy agents. Understanding the cellular and transcriptional mechanisms of response or resistance will aid in prioritization of targets and their clinical translation.
Tm4sf19 deficiency inhibits osteoclast multinucleation and prevents bone loss
Authors: Sujin Park, Jin Sun Heo, Seiya Mizuno, Minwoo Kim, Haein An, Eunji Hong, Min Gi Kang, Junil Kim, Rebecca Yun, Hyeyeon Park, Eun Hye Noh, Min Jung Lee, Kwiyeom Yoon, Pyunggang Kim, Minjung Son, Kyoungwha Pang, Jihee Lee, Jinah Park, Akira Ooshima, Tae-Jin Kim, Je Yeon Park, Kyung-Min Yang, Seung-Jae Myung, Hyun Bae, Kyung-Mi Lee, John Letterio, Seok Hee Park, Satoru Takahashi, Seong-Jin Kim
Journal: Metabolism (2023)

Multinucleation is a hallmark of osteoclast formation and has a unique ability to resorb bone matrix. During osteoclast differentiation, the cytoskeleton reorganization results in the generation of actin belts and eventual bone resorption. Tetraspanins are involved in adhesion, migration and fusion in various cells. However, its function in osteoclast is still unclear. In this study, we identified Tm4sf19, a member of the tetraspanin family, as a regulator of osteoclast function.
Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema
Authors: Huiyang Li, Shuo Liu, Wenjin Dai, Bingmei Yao, Yong Zhou, Sujia Si, Hairong Yu, Riguang Zhao, Fang Jin, Liqun Jiang
Journal: Journal of Controlled Release (2023)
Rationally designed approaches to augment CAR-T therapy for solid tumor treatment
Authors: Chaojie Zhu, Qing Wu, Tao Sheng, Jiaqi Shi, Xinyuan Shen, Jicheng Yu, Yang Du, Jie Sun, Tingxizi Liang, Kaixin He, Yuan Ding, Hongjun Li, Zhen Gu, Weilin Wang
Journal: Bioactive Materials (2023)

Chimeric antigen receptor T cell denoted as CAR-T therapy has realized incredible therapeutic advancements for B cell malignancy treatment. However, its therapeutic validity has yet to be successfully achieved in solid tumors. Different from hematological cancers, solid tumors are characterized by dysregulated blood vessels, dense extracellular matrix, and filled with immunosuppressive signals, which together result in CAR-T cells' insufficient infiltration and rapid dysfunction. The insufficient recognition of tumor cells and tumor heterogeneity eventually causes cancer reoccurrences. In addition, CAR-T therapy also raises safety concerns, including potential cytokine release storm, on-target/off-tumor toxicities, and neuro-system side effects. Here we comprehensively review various targeting aspects, including CAR-T cell design, tumor modulation, and delivery strategy. We believe it is essential to rationally design a combinatory CAR-T therapy via constructing optimized CAR-T cells, directly manipulating tumor tissue microenvironments, and selecting the most suitable delivery strategy to achieve the optimal outcome in both safety and efficacy.
Sickle cell allele <scp><i>HBB</i></scp>‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa
Authors: Hyokyoung G. Hong, Mateus H. Gouveia, Martin D. Ogwang, Patrick Kerchan, Steven J. Reynolds, Constance N. Tenge, Pamela A. Were, Robert T. Kuremu, Walter N. Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Xunde Wang, Jiefu Zhou, Thiago Peixoto Leal, Isaac Otim, Ismail D. Legason, Hadijah Nabalende, Herry Dhudha, Mediatrix Mumia, Francine S. Baker, Temiloluwa Okusolubo, Leona W. Ayers, Kishor Bhatia, James J. Goedert, Joshua Woo, Michelle Manning, Nathan Cole, Wen Luo, Belynda Hicks, George Chagaluka, W. Thomas Johnston, Nora Mutalima, Eric Borgstein, George N. Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M. Molyneux, Robert Newton, Amy Hutchinson, Meredith Yeager, Adebowale A. Adeyemo, Swee Lay Thein, Charles N. Rotimi, Stephen J. Chanock, Ludmila Prokunina‐Olsson, Sam M. Mbulaiteye
Journal: American Journal of Hematology (2023)

Abstract Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma that significantly contributes to childhood cancer burden in sub‐Saharan Africa. Plasmodium falciparum , which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria—such as the sickle cell trait variant, HBB ‐rs334(T)—also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome‐scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB ‐rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628–0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533–0.885; p = .0037). ABO ‐rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379–0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.
Systemic Atrioventricular Valve Surgery in Patients With Congenitally Corrected Transposition of the Great Vessels
Authors: Ahmed A. Abdelrehim, Elizabeth H. Stephens, William R. Miranda, Austin L. Todd, Heidi M. Connolly, Alexander C. Egbe, Luke J. Burchill, Elena A. Ashikhmina, Joseph A. Dearani
Journal: Journal of the American College of Cardiology (2023)
Biofabrication of Composite Bioink‐Nanofiber Constructs: Effect of Rheological Properties of Bioinks on 3D (Bio)Printing and Cells Interaction with Aligned Touch Spun Nanofibers
Authors: Waseem Kitana, Victoria Levario‐Diaz, Elisabetta Ada Cavalcanti‐Adam, Leonid Ionov
Journal: Advanced Healthcare Materials (2023)

Abstract This paper reports on a novel approach for the fabrication of composite multilayered bioink‐nanofibers construct. This work achieves this by using a hands‐free 3D (bio)printing integrated touch‐spinning approach. Additionally, this work investigates the interaction of fibroblasts in different bioinks with the highly aligned touch‐spun nanofibers. This work conducts a comprehensive characterization of the rheological properties of the inks, starting with low‐strain oscillatory rheology to analyze the viscoelastic behavior, when the material structure remains intact. Moreover, this work performs amplitude sweeps to investigate the stability of the inks under large deformations, rotational rheology to examine the shear thinning profile, and a three‐step creep experiment to study time‐dependent rheological behavior. The obtained rheological results are correlated to visual observation of the flow behavior of inks. These behaviors span from an ink with zero‐shear viscosity, very weak shear thinning, and no thixotropic behavior to inks exhibiting flow stress, pronounced shear thinning, and thixotropy. It is demonstrated that inks have an essential effect on cell behavior. While all bioinks allow a preferred directionality of the fibroblasts along the fiber direction, cells tend to form aggregates in bioinks with higher viscosity, and a considerable number of agglomerates are observed in the presence of laponite‐RD.
Advancements in Skin‐Mediated Drug Delivery: Mechanisms, Techniques, and Applications
Authors: Dong Ha Lee, Sunyoung Lim, Sung Soo Kwak, Joohee Kim
Journal: Advanced Healthcare Materials (2023)

Abstract Skin‐mediated drug delivery methods currently are receiving significant attention as a promising approach for the enhanced delivery of drugs through the skin. Skin‐mediated drug delivery offers the potential to overcome the limitations of traditional drug delivery methods, including oral administration and intravenous injection. The challenges associated with drug permeation through layers of skin, which act as a major barrier, are explored, and strategies to overcome these limitations are discussed in detail. This review categorizes skin‐mediated drug delivery methods based on the means of increasing drug permeation, and it provides a comprehensive overview of the mechanisms and techniques associated with these methods. In addition, recent advancements in the application of skin‐mediated drug delivery are presented. The review also outlines the limitations of ongoing research and suggests future perspectives of studies regarding the skin‐mediated delivery of drugs.